U.S. patent number 5,042,501 [Application Number 07/518,010] was granted by the patent office on 1991-08-27 for apparatus and method for analysis of expired breath.
This patent grant is currently assigned to Battelle Memorial Institute. Invention is credited to Thomas J. Kelly, Donald V. Kenny.
United States Patent |
5,042,501 |
Kenny , et al. |
August 27, 1991 |
Apparatus and method for analysis of expired breath
Abstract
Apparatus and method for providing breath for introduction to a
measuring device such as a mass spectrometer. The apparatus
includes a mouthpiece for interfacing a subject with the apparatus;
a tube for carrying exhaled breath from the subject to the inlet of
a mixing chamber; a mixing chamber having an inlet, sample outlet
and exit tube, that provides a residence time for the exhaled
breath sufficient to mix the breath and provide an adequate sample
to the measuring device; and heating apparatus for maintaining the
apparatus above a temperature where condensation of vapor
occurs.
Inventors: |
Kenny; Donald V. (Columbus,
OH), Kelly; Thomas J. (Worthington, OH) |
Assignee: |
Battelle Memorial Institute
(Columbus, OH)
|
Family
ID: |
24062160 |
Appl.
No.: |
07/518,010 |
Filed: |
May 1, 1990 |
Current U.S.
Class: |
600/532 |
Current CPC
Class: |
G01N
33/497 (20130101); A61B 5/097 (20130101); A61B
5/0878 (20130101) |
Current International
Class: |
A61B
5/08 (20060101); A61B 5/087 (20060101); A61B
5/097 (20060101); G01N 33/483 (20060101); H01J
49/04 (20060101); G01N 33/497 (20060101); H01J
49/02 (20060101); A61B 005/097 () |
Field of
Search: |
;128/716,719,725,730 |
References Cited
[Referenced By]
U.S. Patent Documents
|
|
|
4485822 |
December 1984 |
O'Conner et al. |
4850371 |
July 1989 |
Broadhurst et al. |
|
Foreign Patent Documents
Primary Examiner: Kamm; William E.
Assistant Examiner: Akers; Scott R.
Attorney, Agent or Firm: Wiesmann; Klaus H.
Claims
We claim:
1. An apparatus for providing breath from a subject for
introduction to a measuring device comprising:
a. subject interface means for interfacing the subject with the
apparatus;
b. tube means for carrying exhaled breath from the subject
interface means to the inlet of a mixing chamber;
c. a mixing chamber having an inlet, sample outlet and exit tube
means, that provides a residence time for the exhaled breath
sufficient to mix the breath and provide a sufficient sample to the
measuring device; and
d. heating means for maintaining b. and c. above a temperature
where condensation of vapor occurs.
2. The apparatus of claim 1 comprising:
e. adaptor means for introducing sample breath from the mixing
chamber to a measuring device; and
f. additional heating means for maintaining the adaptor means above
a temperature where condensation occurs.
3. The apparatus of claim 1 wherein the heating means includes
means for maintaining the subject interface above the temperature
where condensation of vapor occurs.
4. The apparatus of claim 1 wherein the subject interface means
constitutes a mouthpiece or a tracheotomy tube.
5. The apparatus of claim 1 wherein the tube means has means for
connection to a mass spectrometer.
6. The apparatus of claim 1 wherein the mixing chamber has movable
walls for adjustment of volume.
7. The apparatus of claim 1 wherein the heating means constitutes a
resistance wire and associated control means.
8. The apparatus of claim 1 wherein a calibration device is
connected to the sample outlet to provide standards for the
measuring device.
9. The apparatus of claim 1 wherein the materials that constitute
the breath interface apparatus are inert to the materials to be
tested.
10. A method for measuring trace components in a subject's breath
comprising:
a. providing a subject interface means to obtain breath from the
subject;
b. flowing breath obtained from the subject to a mixing
chamber:
c. mixing the breath in the mixing chamber;
d. flowing breath samples from the mixing chamber to a measuring
device and exiting unneeded breath from the mixing chamber; and
e. maintaining the breath in steps a, b, c, and d above the
condensation temperature of vapor in the breath.
11. The method of claim 10 whereby the residence time is maintained
between about 1 second to about 60 seconds.
12. The method of claim 11 whereby the residence time is maintained
above about 30 seconds.
13. The method of claim 10 whereby the providing step includes a
mouthpiece or a tracheotomy tube as the subject interface.
14. The method of claim 10 whereby the sample flow rate is
maintained between about 0.1 liters per minute to about 100 liters
per minute.
15. The method of claim 14 whereby the sample flow rate is
maintained above about 3 liters per minute.
16. The method of claim 10 comprising:
f. providing a mass spectrometer as the measuring device.
17. The method of claim 10, whereby the system is flushed with
clean air between analysis.
18. The method of claim 10 whereby a calibration standard is
injected into the breath samples from the mixing chamber.
Description
FIELD OF THE INVENTION
The invention serves as an interface between a subject (human or
animal) and a measuring device. The invention differs from prior
art in that whole (i.e. undiluted) breath is analyzed in a realtime
continuous manner. No preanalysis collection or concentration is
needed, and rapid response is achieved. No subject intervention is
needed to control the introduction of breath except to breathe
normally. In one embodiment of the invention for analysis of human
breath, a 3 liter mixing chamber is continuously purged by breath;
by sampling from this chamber at a constant flow rate a continuous
realtime analysis of breath can be performed for clinical
toxicology, occupational medicine and exercise physiology
studies.
BACKGROUND OF THE INVENTION
The assessment of individual personal exposure to toxic substances
is an important component of human and animal health risk
assessment. Assessment of exposure by the analysis of breath is
particularly attractive since it is noninvasive and nontraumatic
for the subject. Breath may also be a less complex medium than
blood or urine, and so may be easier to analyze and characterize.
For these reasons, breath analysis has been applied in several
studies addressing exposure to toxic chemicals, or investigating
natural metabolites such as indicators of disease, see for example:
A. Zlatkis, R. Brazell, and C. Poole, Clin. Chem., 27, 289-297,
1981; B. Krotoszyinski, G. Gabriel, and H. J. O'Neill, Chrom. Sci.,
15, 239, 1977; S. Chen, L. Zieve, and V. Mahadevan, J. Lab. Clin.
Med., 75, 628-635, 1970; M. Simenhoff, J. Burke, J. Saukkonen, A
Ordinavio, and R. Doty, New England J. Med., 297, 132-135, 1977; B.
Lorber, Amer. Rev. Resp. Dis., 112, 875-877, 1975; F. Brugnone, L.
Perbellini, P. Apostoli, and E. Gaffuri, "Monitoring of Industrial
Exposure to Organic Volatile Compounds by Analysis of Alveolar Air
and Blood", American Chemical Society 187th National Meeting, St.
Louis, Mo., 1985; M. Hisamura, Nippon Naika Gakkai Zasshi, 68,
1284-1292, 1979; A. Tangerman, M. T. Meuwese-Arends, J. H. M. van
Tongeren, J. Lab Clin. Med., 106, 175-182, 1985; L. Campbell, D. M.
Marsh, and H. K. Wilson, Ann Occup. Hyg., 31, 121-133, 1987; R. W.
Handy, H. L. Crist, T. W. Stanley, "Quality Assurance For Personal
Exposure Monitoring", in Quality Assurance For Environmental
Measurements, ASTM Special Technical Publication No. 867, 284-296,
1985; and A. W. Jones, G. Maardh, E. Aenggard, Pharmoacol. Biochem.
Behav., 18, 267-272, 1983. In most of the studies breath analysis
has been performed by integrated collection of breath in bags, on
sorbent materials, or in cryogenic traps. Such approaches may
suffer from poor time resolution, inefficient sample collection or
recovery, or sample degradation.
Further, breath analysis is useful in the study of natural
metabolites, including indicators of disease, as well as bodily
effects due to exposure to toxic chemicals. By monitoring whole
breath continuously, in realtime, many studies in chemical
toxicology, occupational medicine and exercise physiology can be
performed.
Recently attempts have been made to apply the considerable
sensitivity and selectivity of tandem mass spectrometry (MS/MS) to
breath analysis, by employing atmospheric pressure chemical
ionization (APCI) as the ionization source, see for example: A. M.
Lovett, N. M. Reid, J. A. Buckley, J. B. French, and D. M. Cameron,
Biomed. Mass Spectrom., 6, 91-97, 1979 F. M. Benoit, W. R.
Davidson, A. M Lovett, S. Nacson, and A. Ngo, Anal. Chem., 55,
805-807, 1983; and F. M. Benoit, W. R. Davidson, A. M. Lovett, S.
Nacson, and A. Ngo, Int. Arch. Occup. Environ. Health, 55, 113-120,
1985. However, such efforts have been limited by the means used to
introduce breath into the mass spectrometer. The breath inlets used
required the subject to control his breath flow rate or an observed
pressure gauge reading during exhalation, required dilution of
breath with a continuous flow of clean air, and provided only
intermittent data (i.e., during each exhalation).
Other relevant art known to the inventors includes the following
U.S. Pat. No.: 4,772,559 to Preti et al. discloses a method of
detecting and diagnosing an individual to determine the presence of
bronchiotic carcinoma by analysis of expired lung air; U.S. Pat.
No. 4,485,822 to O'Connor et al. relates to a system and method for
interfacing a patient with equipment for monitoring gaseous
components of the exhalation of the patient and emphasizes the
elimination of dead space volume and a disc filter for removing
secretions and humidification; U.S. Pat. No. 4,178,919 to Hall
reveals a flowmeter for providing synchronized flow data and
respiratory gas samples to a medical mass spectrometer; U.S. Pat.
No. 4,167,667 to Fletcher, et al. discloses a respiratory gas
moisture separator system for mass spectrometer monitoring systems
that relies on a pressure drop to maintain moisture in the vapor
state and a momentum separator to remove water droplets; U.S. Pat.
No. 3,759,249 to Fletcher, et al. relates to a method and apparatus
for obtaining an analysis of respiratory gas flow rate and
frequency of inspiration and expiration cycles on a "real time"
basis; U.S. Pat. No. 3,649,199 to Littlejohn reveals a method for
detecting trace quantities of an organic drug material in a living
animal and relies on a membrane gas separator for direct breath
analysis (column 3, lines 29-32); U.S. Pat. No. 3,622,278 to
Etzinga discloses a method and means for measuring and analyzing
the composition of alveolar air for determining the volatile
constituents in blood. The device eliminates air from the dead air
spaces of the respiratory tract thereby avoiding dilution of
alveolar air.
An object of the present invention is to provide an improved breath
interface which allows continuous analysis of undiluted breath by
APCI/MS/MS. A further object is to provide an improved breath
interface that reduces the loss of trace constituents in breath to
a minimum. A still further object is to provide an improved breath
interface that is easy to use and reliable.
BRIEF DESCRIPTION OF THE INVENTION
A breath interface apparatus provides breath for introduction to a
measuring device. It consists of subject interface means for
interfacing the subject with the apparatus; tube means for carrying
exhaled breath from the subject interface means to the inlet of a
mixing chamber; a mixing chamber having an inlet, sample outlet and
exit tube means, that provides a residence time for the exhaled
breath sufficient to mix the breath and provide a sufficient sample
to the measuring device; and heating means for maintaining the
apparatus above a temperature where condensation of vapor
occurs.
A method for measuring trace constituents in a subject's breath
encompasses providing a subject interface means to obtain breath
from the subject; flowing breath obtained from the subject to a
mixing chamber; mixing the breath in the mixing chamber; flowing
breath samples from the mixing chamber to a measuring device and
exiting unneeded breath from the mixing chamber; and maintaining
the breath above the condensation temperature of vapor in the
breath and preventing condensation on the apparatus by heating.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a semischematic drawing illustrating details of the
apparatus of the invention.
FIG. 2 is a semischematic drawing depicting exemplary components of
a TAGA (Registered Trademark) instrument useful with the
invention.
FIG. 3 is a semischematic drawing illustrating details of the
apparatus when used with a TAGA instrument as the measuring
device.
FIG. 4 is a drawing of details of a narrow bore inlet tube that is
preferred when using the apparatus with a TAGA instrument.
FIG. 5 is a graph illustrating the response of a TAGA spectrometer
to lactic acid in breath and from a control when used with the
apparatus of the invention.
DETAILED DESCRIPTION OF THE INVENTION
In general, the apparatus of the invention functions as an
interface between a subject and a measuring device. In a preferred
embodiment of the invention the apparatus acts as an interface
between a subject and a mass spectrometer.
The breath interface 100 is shown in FIG. 1 for providing exhaled
breath. A subject uses a conventional mouthpiece 110 (subject
interface means) and breathes normally. One way breathing valves
111,112 (e.g. Hans Rudolph Model 2600) are arranged in relation to
the mouthpiece 110 so that exhaled breath 115 is pushed into the
inlet 116 while inhaled air 113 can be drawn from the room, from
sources of clean air, or from prepared gas mixtures (not shown). By
this means, the air supplied to the subject can be controlled
without hindering the exhalation mechanism. Alternatively, other
apparatus (having the function of a mouthpiece e.g. tracheotomy
tube) known in the art for interfacing with a subject may be used
to obtain a breath sample 115 from the subject. The breath sample
115 is then transported through a large diameter tube 120
(preferably flexible and of Teflon), to inlet tube 130 and past gas
inlet ports 131, and into a mixing chamber 140. The entire flow
system from the mouthpiece 110 to the measuring device 200 is
heated by heating means 170 to prevent condensation of exhaled
water vapor and minimize surface losses of trace substances in the
breath sample. The heated portion is depicted by the shaded area in
FIGS. 1 and 3. If desired, the mouthpiece (subject interface means)
110 may also be heated. The gas inlet ports 131 may be used to
flush the system with zero air, add gaseous standards, or allow the
withdrawal of sample for other tests. The breath sample is drawn
into the measurement device 200 through sample outlet tube 150.
Excess exhaled air 115 is vented at a large bore exit tube 160.
Inlet tube 130 and exit tube 160 preferably extend into the mixing
chamber 140 and preferably have bent portions 13OA,16OA
respectively that are oriented in opposite directions to promote
mixing of the continuous breath sample. Alternatively, baffles (not
shown) could be used at the inlet and exit tubes 130,160 as is
known in the art to promote mixing. Mixing chamber 140 may be of
glass, stainless steel, nickel, Teflon or similar material or other
materials lined with these. Connectors and adaptors may be of
similar materials. If desired the mixing chamber may be of flexible
materials or have movable walls (not shown) to allow adjustment in
volume.
The size of the mixing chamber can be adjusted to obtain a
residence time of about 1 to 60 seconds. At high breath rates the
residence time can be very short whereas at low rates longer
residence times are required to achieve an integrated sample. Flow
rates and size of the mixing chamber are related to the breath rate
provided by the subject. For example, if the subject tested is a
small animal having a low breath rate (e.g. dog, cat, mouse) the
mixing chamber and flow rate are scaled down to provide proper
residence times and sample flow rates. Sample flow to the TAGA must
be adjusted to be lower than the lowest flow of breath from the
subject to preserve sample integrity. Exhaust vacuum at sample
outlet 212 can be adjusted to accommodate high or low flow rates.
Flow rates may be as low as about 0.1 liters/minute and as high as
about 100 liters/minute.
Heating means 170 uses preferably resistance wire heating and
associated control means where the heating wires are wound around
or placed over the surfaces to be heated. Additionally, insulation
(not shown) may be used in conjunction with heating means 170 if
needed or desired for better control. It is the use of heating
means 170 that provides the desired reduction in the loss of trace
constituents of sampled breath by preventing condensation of
vapor.
Exhaled breath is normally saturated with water vapor (100 per cent
relative humidity). The exhaled breath is also normally at or very
near body temperature. For humans this temperature is about 37 C.
(98.6 F.), but will vary for each subject. Thus, the heating means
must maintain all parts of the apparatus in contact with expired
breath above the temperature where condensation would occur. These
temperature relationships can easily be determined by those skilled
in the art. It is preferred that a temperature slightly higher than
the subjects body temperature be used.
The prevention of condensation is important since any condensate
will remove trace components from the sampled breath and give false
readings. Of similar importance is the need to provide materials or
lining for the tubing, connectors, mixing chamber, etc. that will
not absorb, adsorb or otherwise react with breath components.
The measuring device 200 used in the examples below was a TAGA mass
spectrometer 201 (Model 6OOOE), an atmospheric pressure chemical
ionization (APCI) tandem mass spectrometer. It is a sensitive,
specific, fast, and versatile analyzer for air analysis. Components
of the TAGA 201 are illustrated in FIG. 2. The basic components are
the inlet module 210, ionization source 220, transfer ion lenses
230, three quadruple mass filters 241, 242, 243, and the detector
250. Samples of air streams are introduced at sample inlet 211 and
exhausted at sample exhaust 212. Trace contaminants in the sampled
air stream are ionized by a corona discharge 214 at atmospheric
pressure. Ionized molecules are electrically accelerated through a
counter current flow of dry nitrogen 215 toward a small orifice 216
where they are carried into a cryogenic vacuum system 217 by a
small flow of nitrogen gas. The ion transfer lenses 231 eliminate
the majority of the nitrogen gas while electrically focusing the
ions into the first quadruple mass analyzer 241. The first
quadruple 241 typically functions as a mass filter by eliminating
all but those ions of a specific mass of interest. The mass of
interest is selected to correspond to a molecular ion of a
particular contaminant which may also include molecular or fragment
ions of interfering species. Ions passing through the first
quadruple 241 are accelerated into the second quadruple 242 where
they are intercepted by a neutral beam of argon 219 or other inert
gas atoms. Collision with argon atoms at region 221 results in
fragmentation of the ions in a predictable manner characteristic of
their molecular structure. Fragments resulting from the molecular
ion of interest are then sorted out from fragments of interfering
ions by the third quadruple 243 mass analyzer. As a result of the
tandem mass analyzers, the TAGA achieves a highly specific
measurement for a given combination of mass analyzer settings. The
TAGA can monitor several specific target compounds simultaneously
or can scan a mass range for compounds which have a common
structural feature. Conventional scanning modes provide information
for the identification of unknowns.
When a TAGA spectrometer 201 is used for example with a human
subject, samples are removed from the mixing chamber 140 by way of
outlet tube 150 at a constant flow of about 3 L/min. This is
greatly reduced from the typical TAGA flow of 30-100 L/min used in
atmospheric sampling.
Referring to FIG. 3, an adaptor 310 provides for connection to
outlet tube 150, the sample inlet tube 400 to the TAGA, and
vaporizer probe 320 with unions 311,312 and cap 313. The original
sample inlet tube to the TAGA is replaced by a narrow bore sample
inlet tube 400 which enhances sensitivity in breath analysis by
more efficiently directing sample flow into the ionization region
214. The liquid vaporizer probe 320 is supplied by an external
calibration source, a syringe drive 330 is depicted, that delivers
calibration solutions into the TAGA sample flow that flows from
tube 150 through connector 310 to sample inlet tube 400, allowing
standard additions to the breath sample without interrupting
analysis. In the examples herein aqueous lactic acid solutions of
10 .sup.-4 M were used for calibration. A human adult subject even
at rest can easily supply more than the 3 L/min flow required by
the TAGA as configured in the preferred embodiment for human
subjects as described herein; the large bore exit tube 160 allows
excess breath to be diverted with negligible flow restriction. This
exit tube 160 can also be used to supply breath for other
tests.
The apparatus and method may be adapted to other mass spectrometers
by controlling the flow of sample gases. For example, with the TAGA
it does not matter if water vapor is in the sample. With other mass
spectrometers this may be a problem and the water vapor will have
to be removed. This will not work as well since trace species will
be removed with the water.
FIG. 4 provides details of the inlet tube 400. The inlet tube 400
is secured to the system by a threaded connection 401 that provides
support and seals the TAGA 201 and adaptor 310 with union 312. The
inlet tube comprises an inner tube 403 and outer tube 404. The
inner tube 403 is sealed at one end 405 to outer tube 404 while
Teflon ring 402 provides for support between tubes 403,404 at their
other ends and seals the space 406 between them. The diameter of
the bore 407 in tube 403 is reduced to 6 mm from that of the inlet
tube normally used in the TAGA 201. This reduction in the tube size
provides improved transport of the breath flow into the ionizing
region 214 of the TAGA 201, resulting in a sensitivity about five
(5) times higher than that obtained with the larger tube.
Nonionized sample then exits the TAGA through outlet 212 to a pump
(not shown). Ions from the sample proceed to detection as described
above. The inner tube 403 is heated by heating tape or similar
auxiliary heating means 408 that is connected to heating means 170
by connector 409.
The diameter of bore 407 may be further adjusted to accommodate
lower flows other than those used with the human subjects described
herein. Small mammals, for example, would require much smaller
bores to improve sensitivity by improved transfer of sample into
the ionization region 214. These can easily be determined by those
skilled in the art having read the teachings herein.
The breath interface 100 has undergone a variety of tests. Heating
of the breath flow path prevents condensation of breath moisture at
breath flow rates from 5 to over 100 L/min, characteristic of
subject activity levels ranging from rest to vigorous exertion.
Calibrations have been performed using several different procedures
in addition to the normal mode of calibration described above. The
additional calibration tests have shown the same results when the
calibration probe is positioned upstream of the breath interface
100 as when it is positioned in the normal downstream position (see
FIG. 3). These tests have also shown no effect of flow rate in the
breath interface 100 on TAGA response. Further tests using
humidified air have disclosed no transient effects due to the
introduction of humidity into the inlet, as occurs at the onset of
breathing into the device. However, these tests and calibration
procedures have shown that TAGA sensitivity to lactic acid in
breath or in air with 100 percent humidity is reduced by about 30
percent relative to that in dry air. This finding indicates the
need to calibrate by standard addition to the breath matrix, a
capability which is built into the apparatus described herein.
As an example for detection of trace substances in breath, lactic
acid has been monitored continuously in breath over time periods
from a few minutes up to nearly an hour, during exercising of a
human subject on a stationary bicycle. FIG. 5 shows an example of
monitoring lactate in breath during a brief exercise period (time
(t) in minutes on the x axis and intensity (I) in ion counts per
second on the y axis). Lactic acid is detected by monitoring of
daughter ions of masses 45 (solid line) and 43 (dotted line)
arising from the fragmentation of lactate anion (mass 89). The
graph shows the following periods as noted at the bottom
thereof:
A. background, zero air
B. subject started breathing into inlet
C. 8.2 ppb standard addition with syringe drive introduction of
lactic acid
D. subjects breath only, syringe drive off
E. zero air flush of system.
The subject began breathing into the mouthpiece 110 at rest, and
after a short time began exercising on a stationary bicycle,
continuing for several minutes until moderate exertion and
resulting increased breath rate were reached. While the subject was
exercising, lactic acid response was calibrated by standard
addition to the breath flow. Then the subject stopped exercising,
and finally the system was flushed with clean purified air.
Response to the breath concentration of lactic acid was seen within
five seconds once the subject started breathing into the system. An
approximately steady state was quickly established with no evidence
of variation of signal due to the breathing cycle.
Also of interest in FIG. 5 are data from the end of the experiment.
Region E shows a sharp decline in signal when the system is flushed
with clean air and breath analysis ends. The lactic acid signal in
zero air drops rapidly to that seen before the breath analysis,
indicating little memory effect in the breath interface 100.
A standard addition of lactic acid to the breath flow is
superimposed upon the breath lactate signal in FIG. 5; the spike at
the start of calibration is due to instability in the syringe
drive/vaporizer system when first turned on. Lactate concentrations
in breath shown in FIG. 5 and observed in other tests are a few
ppbv, consistent with calculations based on the pKa and Henry's law
constant for lactic acid, roughly millimolar concentrations of
lactate in blood, and a pH for body fluids of about 7. Acetic and
pyruvic acids were also monitored in some tests, and were present
at concentrations well below those of lactic acid. The continuous
and stable response shown in FIG. 5, which contrasts with the
results of the prior art employing APCI/MS/MS in which measurements
were made only on individual exhalations. The lactate concentration
in whole breath was generally observed to remain constant or to
decrease during the exercise tests as breathing rate increased.
However, calculations incorporating breath flow rate indicate that
the total output of lactate in breath increased greatly during
exercise, parallel to the power output of the subject. The amounts
of lactic acid excreted in breath are negligibly small compared to
the total amount of lactic acid in other reservoirs within the
body; however, these tests on breath lactate serve to illustrate
the use of the device in breath analysis for industrial hygiene
tests, hazardous material exposure studies, bioresponse tests,
pharmaceutical kinetic studies, and disease detection. For example,
workers in a chemical plant would be monitored for chemicals they
were exposed to such as organic solvents (benzene, toluene and the
like); human or animal subjects would be monitored to determine
metabolism of foods (e.g. breath fresheners, artificial
sweeteners); human or animal subjects would be monitored for the
metabolism of drugs in the body versus time (e.g. anesthetics);
subjects would be monitored for detection of compounds indicative
of disease (e.g. sulfur compounds in liver disfunction), or to
determine levels of various compounds such as ammonia or acetone
indicative of various body states, and so on.
The breath interface 100 requires no attention from the subject,
and thus is applicable to subject activity ranging from rest to
extreme exercise for a great latitude in breathing rates. The
apparatus is useful for the flow rates indicated above.
While the forms of the invention herein disclosed constitute
presently preferred embodiments, many others are possible. It is
not intended herein to mention all of the possible equivalent forms
or ramifications of the invention. It is to be understood that the
terms used herein are merely descriptive rather than limiting, and
that various changes may be made without departing from the spirit
or scope of the invention.
* * * * *